Latest MS Research News

Intricate niche of cells and tissues in the brain may be fueling inflammation in progressive MS

December 14, 2015

Canadian Study

MS Society Funded

Background

The disease process underlying progressive MS remains a complex,
largely unsolved area of research. People living with progressive
MS often respond poorly to current MS immune-modifying therapies,
suggesting that progressive MS is less an inflammatory disease
and more a neurodegenerative disease.

In relapsing-remitting MS, inflammation appears to play a much
more prominent role; however, new research evidence is surfacing
which shows that inflammation may also be involved in progressive
MS, albeit in a different way. Researchers postulate that
inflammatory cells may be “setting up shop” inside the brain,
causing ongoing damage to nerve cells. This could explain
neurodegeneration in progressive MS, and researchers from the
University of Toronto led by Dr. Jennifer Gommerman have provided
compelling findings supporting this possibility. Their study,
funded by the MS Society of Canada and MS Scientific Research
Foundation, was published this month in the journal Immunity. Lead author of the paper,
Dr. Natalia Pikor, was a recipient of an MS Society Doctoral
Award.

Study Methods and Results

The study involved mice that exhibited MS-like symptoms, as well
as blood cells extracted from people living with MS and non-MS
controls. In the mice, researchers observed the location and
composition of so-called “tertiary lymphoid tissues”, which are a
collection of white blood cells that they believe are residing
within the brain and contributing to harmful inflammation in MS.
In particular they looked within the meninges, the part of the
brain that appears to be rich in inflammatory
B cells in people with progressive MS.

In mice they found that, at the start of the disease,
T cells dominated within the meninges, and at the peak of the
disease, there was a mix of B and T cells. Specifically, they
found that T helper 17 or Th17 cells (a type of T cell)
were highly active in this area of the brain, causing
demyelination. This echoes previous studies showing that Th17
cells are major players in autoimmune disease.

Using the same mice they looked at changes in the cellular
environment within the meninges. They discovered the formation of
a network of supportive fibers, which created a net that can
collect more Th17 cells and preserve inflammation. When analyzing
human blood samples, the researchers found increased levels of
inflammatory cytokines that are associated with Th17 cells. This
confirmed the mouse findings and linked them to the human
disease.

Comment

For years it was demonstrated that, in MS, immune cells are
activated outside of the
central nervous system (CNS), and then travel into the CNS
where they cause damage. New research shows that inflammation may
also be occurring within the CNS, independent of the new waves of
immune cells coming in. In their latest study funded by the MS
Society, Dr. Gommerman and her team provide a detailed
description of this compartmentalized inflammation that could
help explain what happens in progressive MS.

Overall, the study strengthens the MS research community’s
understanding of the inflammatory nature of MS, by identifying
where exactly inflammation is taking place and how it is
maintained. The MS Society looks forward to seeing how this work
will inform development of therapies for progressive MS that
block the effects of culprits such as the Th17 cells.